17(R)‐Resolvin D1 differentially regulates TLR4‐mediated responses of primary human macrophages to purified LPS and live E. coli

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: eicosanoid;    TNF;    IL‐;    6;    resolution of inflammation;   

DOI  :  10.1189/jlb.0311145

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Detectionandclearanceofbacterialinfectionrequirebalancedeffectorandresolutionsignalstoavoidchronicinflammation.DetectionofGNBLPSbyTLR4onmϕinducesinflammatoryresponses,contributingtochronicinflammationandtissueinjury.LXsandRvsareendogenouslipidmediatorsthatenhanceresolutionofinflammation,andtheiractionsonprimaryhumanmϕresponsestowardGNBarelargelyuncharacterized.Here,wereportthatLXA4,LXB4,andRvD1,testedat0.1–1μM,inhibitedLPS‐inducedTNFproductionfromprimaryhumanmϕ,withATLand17(R)‐RvD1,demonstratingpotentinhibitionat0.1μM.Inaddition,17(R)‐RvD1inhibitedLPS‐inducedprimaryhumanmϕproductionofIL‐7,IL‐12p70,GM‐CSF,IL‐8,CCL2,andMIP‐1αwithoutreducingthatofIL‐6orIL‐10.Remarkably,whenstimulatedwithliveEscherichiacoli,mϕtreatedwith17(R)‐RvD1demonstratedincreasedTNFproductionandenhancedinternalizationandkillingofthebacteria.17(R)‐RvD1‐enhancedTNF,internalization,andkillingwerenotevidentforanlpxMmutantofE.coliexpressinghypoacylatedLPSwithreducedinflammatoryactivity.Furthermore,17(R)‐RvD1‐enhanced,E.coli‐inducedTNFproductionwasevidentinWTbutnotTLR4‐deficientmurinemϕ.Thus,RvsdifferentiallymodulateprimaryhumanmϕresponsestoE.coliinanLPS‐andTLR4‐dependentmanner,suchthatthisRvcouldpromoteresolutionofGNB/LPS‐driveninflammationbyreducingmϕproinflammatoryresponsestoisolatedLPSandincreasingmϕresponsesimportantforclearanceofinfection...

【 授权许可】

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